title: Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer.
abstract: BACKGROUND
  Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT).
  
  
  METHODS
  Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m(2) followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5mg/m(2) per level.
  
  
  RESULTS
  Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m(2) and 45 mg/m(2)), carboplatin (AUC=2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m(2) and carboplatin, AUC=2). At Level 2 (paclitaxel, 45 mg/m(2) and carboplatin, AUC=2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m(2) and 40 mg/m(2), respectively.
  
  
  CONCLUSIONS
  This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m(2) at AUC=2, respectively. Further studies are warranted to evaluate the efficacy of this regimen.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakakibara-Konishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Naofumi
authors.initials: N
authors.lastname: Shinagawa
authors.forename: Junko
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Norio
authors.initials: N
authors.lastname: Katoh
authors.forename: Rikiya
authors.initials: R
authors.lastname: Onimaru
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D016190:Carboplatin; D017239:Paclitaxel